COVID-19 Clinical Trials

Sanjay Sethi MDProfessor and Division Chief

Pulmonary, Critical Care and Sleep Medicine

Assistant Vice President for Health Sciences

Director, Clinical Research office

Deputy Director, Clinical and Translational Science Institute

University at Buffalo, SUNY

ssethi@buffalo.edu

COVID-19 Pathogenesis

COVID-19 Potential Interventions

CP

ImmunomodulatorsSarilumab

AntiviralsRemdesivir

Figure 1

The Lancet DOI: (10.1016/S0140-6736(20)31180-6)

Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis M Mehra et al, The Lancet DOI: 10.1016/S0140-6736(20)31180-6

Remdesivir: Local Results

• Expanded access program (EAP)

• N=4

• Baseline severity: All intubated

• Outcomes• 1 died

• 2 extubated

• 1 intubated

• Emergency use authorization (EUA)

• Gilead donated 144,000 courses of Remdesivir

• Substantial increase in supply

• Can be used in earlier disease

Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital

with COVID-19: an open-label, randomised, phase 2 trial Prof Ivan Fan-Ngai Hung, The Lancet DOI: 10.1016/S0140-6736(20)31042-4

Convalescent Plasma: Mayo/BARDA Program

Convalescent Plasma: Safety and ?Efficacy

Convalescent Plasma: Safety and ?Efficacy

Convalescent Plasma: Safety and ?Efficacy

Convalescent plasma; Local Results

Sarilumab: Anti-IL6 Inhibitor

Sarilumab: Local Results

• 18 patients randomized

• 17 of 18 were intubated at baseline

• MFS: 6 patients• 4 discharged, 2 died

• ECMC: 8 patients• 1 discharged, 7 still intubated

• BGH: 4 patients• 3 discharged, 1 died

New Trials

• Apellis

• Covis

Planned Trials

• Adjunctive Photobiomodulation (PBM) treatment to prevent progression of COVID-19 in hospitalized patients. • Arany and Sethi co-PIs

• A Pilot Randomized, Double-Blind, Placebo-Controlled Clinical Trial of the Safety and Efficacy of Melatonin for the Treatment of COVID-19 in OutPatients• Dubocovich and Sethi co-PIs

• The use of non-specific HOST protective effects of oral polio vaccine to prevent COVID-19 (SHIELD Trial) • Morse, Hicar, Gomez co-Is

Trials Being Considered

• Monoclonal antibodies for prophylaxis

• Monoclonal antibodies for treatment

• Immunomodulation

• Vaccine trials

• Need Investigators

• Need Research coordinators

• ‘With challenges, come opportunities’

COVID: Multimodality Therapy

• Prevention• Vaccination• Control Risk Factors• Immune enhancement (Vitamin D)• Monoclonal antibodies

• Outpatient• Antiviral (Ivermectin)• Immunomodulation (Melatonin, Ciclesonide)• ?Convalescent plasma • ?Monoclonal Antibodies

• Inpatient• Antiviral• Convalescent plasma• Immunomodulation• Block cytokine storm

Acknowledgements

• Clinical Research Office• Pam Anderson• Kim Brunton• Lynn Jagodzinski• Conor Flynn

• CTSA• Tim Murphy

• Office Of Research Compliance• Rich Karalus• Stan Halverson

• Kaleida Health• Ken Snyder• Ashlee Lang

• ECMC• Brian Murray• Sally Algera

• Research coordinators• Catherine Wrona• Ryan Haley• Judith Wilkins• Nancy Desu• Deanna Coleman• Chris Roach

• RPCCC Donor Center• Joanne Becker• Maria Turner

• JSMBS• Daniel Zinkovsky

(MS3)

• Investigators• Jamie Nadler

• Manoj Mammen

• John Crane

• Joseph Izzo

• Kim Zammit

• Carla Frederick

• Alberto Monegro

• Karin Provost

• Archana Mishra

• Brian Clemency